Endotoxin Is Not Essential for the Development of Cockroach Induced Allergic Airway Inflammation

PURPOSE: Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice. MATERIALS AND METHODS: Airway allergic inflammation was induced by intranasal administration of either CR extract, CR with additional endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR-4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice. RESULTS: Intranasal administration of CR extracts significantly induced airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and goblet cell hyperplasia of respiratory epithelium; however, it did not affect the development of AHR. Endotoxin depletion in CR extract did not attenuate eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13 expression in the lungs compared to CR alone. The attenuation of AHR, eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract alone was not different between TLR-4 mutant and the wild type mice. In addition, heat inactivated CR extract administration induced attenuated AHR and eosinophilic inflammation. CONCLUSION: Endotoxin in CR extracts may not be essential to the development of airway inflammation.

Effect of ozone on response to ovalbumin & its modulation by vitamins C & E in sensitized guinea pigs.

Background & objectives: Exposure to ozone and asthma are both associated with increased oxidative stress. Exposure to ozone therefore, may potentiate the airway response to allergens. We undertook this study to investigate the effect of ozone exposure on airway response to ovalbumin in sensitized guinea pigs and its modulation by dietary supplementation with antioxidant vitamins C and E. Methods: After in vivo measurements of specific airways conductance (SGaw) and airway hyperresponsiveness (AHR) to inhaled histamine, guinea pigs were sensitized to ovalbumin and divided into three groups: (i) sensitized; (ii) sensitized and exposed daily to ozone; and (iii) sensitized, exposed daily to ozone and given dietary supplementation with vitamin C, 2 mg/kg body wt and E, 7 IU/kg body wt. A control group of nonsensitized animals was included. After 4 wk, AHR was measured again and animals were challenged with inhaled ovalbumin. Changes in SGaw were followed for early and late airway bronchoconstrictive responses. The following measurements were obtained: (i) parameters of oxidative stress - plasma malonaldehyde (MDA) as marker of lipid peroxidation and superoxide anion generation by leukocytes and bronchoalveolar lavage (BAL) cells; (ii) antioxidant status: red cell superoxide dismutase (SOD); and (iii) glutathione peroxidase (GPx). BAL cytology was studied. Results: Ozone exposure resulted in an increase in AHR and early and late bronchoconstrictive responses after ovalbumin challenge, greater superoxide anion generation in BAL cells, higher plasma MDA levels and decrease in red cell SOD activity. Dietary supplementation with vitamin C and E prevented or ameliorated these responses. Interpretation & conclusions: Exposure to ozone at concentrations of 0.12 ppm for 2 h daily for 4 wk enhances the airway response to allergens in sensitized guinea pigs. Dietary supplementation with antioxidant vitamins E and C, affords variable degree of protection against this enhancement.

Additive Effect of Diesel Exhaust Particulates and Ozone on Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

Allergic airway diseases are related to exposure to atmospheric pollutants, which have been suggested to be one factor in the increasing prevalence of asthma. Little is known about the effect of ozone and diesel exhaust particulates (DEP) on the development or aggravation of asthma. We have used a mouse asthma model to determine the effect of ozone and DEP on airway hyperresponsiveness and inflammation. Methacholine enhanced pause (P(enh)) was measured. Levels of IL-4 and IFN-gamma were quantified in bronchoalveolar lavage fluids by enzyme immunoassays. The OVA-sensitized-challenged and ozone and DEP exposure group had higher P(enh) than the OVA-sensitized-challenged group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone exposure group. Levels of IFN-gamma were decreased in the OVA-sensitized-challenged and DEP exposure group and the OVA-sensitized-challenged and ozone and DEP exposure group compared to the OVA-sensitized-challenged and ozone exposure group. Levels of IL-4 were increased in the OVA-sensitized-challenged and ozone exposure group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone and DEP exposure group compared to OVA-sensitized-challenged group. Co-exposure of ozone and DEP has additive effect on airway hyperresponsiveness by modulation of IL-4 and IFN-gamma suggesting that DEP amplify Th2 immune response.

Asociación entre exposición a polvo de soja, sensibilidad alérgica y perfil de síntomas respiratorios / [Association between soybean dust exposure, allergic sensitivity and profile of respiratory symptoms]

The purpose of this study was to correlate soybean dust (SD) exposure, skin reactivity to soybean hull (SH) allergens, and symptoms of asthma and/or allergic rhinitis. A group of 365 subjects with asthma and/or allergic rhinitis and a control group of 50 individuals without respiratory symptoms were studied. The level of exposure to SD is defined as follows: 1) direct (DE); 2) indirect (ID), and 3) urban (UE). All subjects completed standard questionnaires. Skin tests with a SH extract and with common allergens were performed by the prick technique (SPT). Fifty-six (15.3

) patients and no subjects from control group had positive SPT (histamine index > or = 0.5) with a SH allergen extract. The percentages of positive SPT to SH extract were 38.7

in subjects with DE, IE and UE, respectively (p < 0.001). Monosensitization to SH was absent in all subjects. The percent of subjects with positive SPTs to mites (p < 0.01), pollen (p < 0.01) and molds (p < 0.05) were higher in subjects with a positive SPT to SH versus those with a negative SPT to SH. Sixty-six percent of subjects with DE and 13.6

of subjects with IE or UE reported respiratory symptoms after SD inhalation (Odds Ratio: 12.67 [2.4-74.9], p < 0.001). Compared to subjects exclusively sensitized to mites, patients sensitized to SH presented significantly different clinical characteristics. Soybean production has been increasing in Argentina during the last 20 years, determining an increase in the population exposed to chronic SD inhalation. This fact determines a high risk of sensitization and triggering of respiratory symptoms in atopic subjects. This study demonstrates that there is: 1) a high prevalence of skin reactivity to SH in subjects with asthma and/or allergic rhinitis from Argentina and that this prevalence is associated with the level of exposure to SD, and 2) an association between sensitivity to SH and severity of asthma. Measures to avoid release and inhalation of SD in rural areas from Argentina are needed.